Effect of quinolinic acid on gene expression in human astrocytes: Implications for Alzheimer's disease

Ka Ka Ting , Bruce J. Brew , Gilles J. Guillemin
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引用次数: 9

Abstract

Activated microglia and astrocytes play a key role in the neuroinflammatory response during Alzheimer's disease (AD). The kynurenine pathway (KP) of tryptophan degradation is activated and production of the excitotoxin quinolinic acid (QUIN) by monocytic cells is increased. We studied here the effects of QUIN in pathophysiological concentrations on the expression of genes including IL-1β, IL-6, S100β, Glutamate synthetase (GS) glial fibrillary acidic protein (GFAP) that are commonly associated with astrocytes in the development of neuroinflammation in AD. We found that IL-6, S100β and GS genes were constitutively expressed in human adult astrocytes (HAA) and only with TNFα, but not QUIN, IL-6 and S100β expression were increased compared with controls in HAA. IL-1β expression was increased by IFN-γ, TNFα and QUIN in HAA. These preliminary results suggest that QUIN's role in astroglial inflammatory response is mediated by increase of IL-1β expression. Therefore, QUIN is likely to play a role in astroglial inflammatory response that may contribute to the pathogenesis of AD.

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喹啉酸对人类星形胶质细胞基因表达的影响:对阿尔茨海默病的影响
激活的小胶质细胞和星形胶质细胞在阿尔茨海默病(AD)期间的神经炎症反应中发挥关键作用。色氨酸降解的犬尿氨酸途径(KP)被激活,单核细胞产生兴奋毒素喹啉酸(QUIN)增加。我们在此研究了病理生理浓度的QUIN对IL-1β、IL-6、S100β、谷氨酸合成酶(GS)胶质纤维酸性蛋白(GFAP)等基因表达的影响,这些基因在AD神经炎症的发展中通常与星形胶质细胞相关。我们发现IL-6、S100β和GS基因在人成人星形胶质细胞(HAA)中组成性表达,仅与TNFα表达,而QUIN基因不表达,IL-6和S100β的表达在HAA中与对照组相比增加。在HAA中,IFN-γ、tnf - α和QUIN均升高IL-1β的表达。这些初步结果表明,QUIN在星形胶质细胞炎症反应中的作用是通过IL-1β表达增加介导的。因此,QUIN可能在星形胶质细胞炎症反应中发挥作用,可能参与AD的发病机制。
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